A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis

the BLING II study

Joel Dulhunty, Jason Roberts, Joshua Davis, Steven Webb, Rinaldo Bellomo, Charles Gomersall, Charudatt Shirwadkar, Glenn Eastwood, John Myburgh, David Paterson, Therese Starr, Andrew Udy, Sanjoy Paul, Jeffrey Lipman

    Research output: Contribution to journal › Comment/debate › Research

    Abstract

    Background and rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of beta-lactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. Design, settings, participants and interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin-tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. Main outcome measures: The primary outcome is ICU-free days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. Results and conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.
    Original languageEnglish
    Pages (from-to)179-185
    Number of pages7
    JournalCritical Care and Resuscitation
    Volume15
    Issue number3
    Publication statusPublished - 2013

    Fingerprint

    beta-Lactams
    Critical Illness
    Sepsis
    Randomized Controlled Trials
    Anti-Bacterial Agents
    meropenem
    Ticarcillin
    Clavulanic Acid
    Survival
    Bacteremia
    Sample Size
    Intensive Care Units
    Pharmacokinetics
    Outcome Assessment (Health Care)

    Cite this

    Dulhunty, Joel ; Roberts, Jason ; Davis, Joshua ; Webb, Steven ; Bellomo, Rinaldo ; Gomersall, Charles ; Shirwadkar, Charudatt ; Eastwood, Glenn ; Myburgh, John ; Paterson, David ; Starr, Therese ; Udy, Andrew ; Paul, Sanjoy ; Lipman, Jeffrey. / A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis : the BLING II study. In: Critical Care and Resuscitation. 2013 ; Vol. 15, No. 3. pp. 179-185.
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    abstract = "Background and rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of beta-lactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. Design, settings, participants and interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin-tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. Main outcome measures: The primary outcome is ICU-free days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. Results and conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.",
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    author = "Joel Dulhunty and Jason Roberts and Joshua Davis and Steven Webb and Rinaldo Bellomo and Charles Gomersall and Charudatt Shirwadkar and Glenn Eastwood and John Myburgh and David Paterson and Therese Starr and Andrew Udy and Sanjoy Paul and Jeffrey Lipman",
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    Dulhunty, J, Roberts, J, Davis, J, Webb, S, Bellomo, R, Gomersall, C, Shirwadkar, C, Eastwood, G, Myburgh, J, Paterson, D, Starr, T, Udy, A, Paul, S & Lipman, J 2013, 'A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis: the BLING II study', Critical Care and Resuscitation, vol. 15, no. 3, pp. 179-185.

    A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis : the BLING II study. / Dulhunty, Joel; Roberts, Jason; Davis, Joshua; Webb, Steven; Bellomo, Rinaldo; Gomersall, Charles; Shirwadkar, Charudatt; Eastwood, Glenn; Myburgh, John; Paterson, David; Starr, Therese; Udy, Andrew; Paul, Sanjoy; Lipman, Jeffrey.

    In: Critical Care and Resuscitation, Vol. 15, No. 3, 2013, p. 179-185.

    Research output: Contribution to journal › Comment/debate › Research

    TY - JOUR

    T1 - A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis

    T2 - the BLING II study

    AU - Dulhunty, Joel

    AU - Roberts, Jason

    AU - Davis, Joshua

    AU - Webb, Steven

    AU - Bellomo, Rinaldo

    AU - Gomersall, Charles

    AU - Shirwadkar, Charudatt

    AU - Eastwood, Glenn

    AU - Myburgh, John

    AU - Paterson, David

    AU - Starr, Therese

    AU - Udy, Andrew

    AU - Paul, Sanjoy

    AU - Lipman, Jeffrey

    PY - 2013

    Y1 - 2013

    N2 - Background and rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of beta-lactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. Design, settings, participants and interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin-tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. Main outcome measures: The primary outcome is ICU-free days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. Results and conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.

    AB - Background and rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of beta-lactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. Design, settings, participants and interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin-tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. Main outcome measures: The primary outcome is ICU-free days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. Results and conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.

    KW - beta lactam

    KW - adult

    KW - aged

    KW - article

    KW - comparative study

    KW - controlled clinical trial

    KW - controlled study

    KW - critical illness

    KW - dose response

    KW - double blind procedure

    KW - female

    KW - follow up

    KW - human

    KW - intensive care

    KW - intravenous drug administration

    KW - male

    KW - methodology

    KW - middle aged

    KW - multicenter study

    KW - phase 2 clinical trial

    KW - prospective study

    KW - randomized controlled trial

    KW - sepsis

    KW - treatment outcome

    KW - Adult

    KW - Aged

    KW - beta-Lactams

    KW - Critical Care

    KW - Critical Illness

    KW - Dose-Response Relationship, Drug

    KW - Double-Blind Method

    KW - Female

    KW - Follow-Up Studies

    KW - Humans

    KW - Infusions, Intravenous

    KW - Male

    KW - Middle Aged

    KW - Prospective Studies

    KW - Sepsis

    KW - Treatment Outcome

    M3 - Comment/debate

    VL - 15

    SP - 179

    EP - 185

    JO - Critical Care and Resuscitation

    JF - Critical Care and Resuscitation

    SN - 1441-2772

    IS - 3

    ER -

    Dulhunty J, Roberts J, Davis J, Webb S, Bellomo R, Gomersall C et al. A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis: the BLING II study. Critical Care and Resuscitation. 2013;15(3):179-185.

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